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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 451 records · Page 25Linked to original sources

Application of in vivo microdialysis to transdermal absorption of methotrexate in rats.

Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 microL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06 +/- 0.04 microM in the control to 56 +/- 26 microM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.

Administration, Cutaneous↗

Effects of ryanodine on development of myogenic response in rat small skeletal muscle arteries.

OBJECTIVE: The aim was to elucidate the functional role of the sarcoplasmic reticulum in myogenic contraction. METHODS: Small arteries which perfuse the rat gracilis muscle were isolated and cannulated. The inner diameter was measured under no flow condition. Myogenic contraction was induced by increasing transmural pressure from 40 to 100 mm Hg. The diameter transient and the steady state internal diameter were analysed at 40 (ID40) and 100 mm Hg (ID100) of lumen pressure. RESULTS: In control, the vessels dilated immediately after the pressure change, and then constricted over approximately 4 min (the diameter decay). ID40 and ID100 were 120(SEM 16) and 108(12) microns (n = 6, p < 0.05), respectively. Ryanodine (10(-5) M) decreased ID40 to 82(8) microns. The relative rate of the diameter decay in the first 1 min was lower in the ryanodine treated vessels than in control, at 43(1)% v 74(7)%, n = 6 (p < 0.05). While KCl constriction was similar to that of ryanodine, the diameter decay was identical to that of control. Thus a decrease in baseline diameter was not of itself the cause of the depressed rate of diameter decay in the ryanodine treated vessels. Nisoldipine (10(-6) M) abolished myogenic contraction. CONCLUSIONS: Ryanodine sensitive sarcoplasmic reticular function is probably involved in the mechanism for developing the myogenic response in rat skeletal muscle small arteries.

Animals↗

Effects of protein kinase C activator and inhibitor on adrenal catecholamine release in response to splanchnic nerve stimulation in anesthetized dogs.

Effects of protein kinase C (PKC) activator and inhibitors on adrenal catecholamine release were examined in anesthetized dogs. Output of epinephrine (EPI) and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. All drugs were infused intraarterially (i.a.) into the adrenal gland through the phrenic abdominal artery. Infusion of the PKC activator phorbol-12,13-dibutyrate (PDB 0.1 micrograms/min) increased EPI and NE output during basal state and enhanced increases in catecholamine output induced by splanchnic nerve stimulation (SNS 1 and 3 Hz). These effects of PDB were abolished by the PKC inhibitor staurosporine (SSP 0.3 microgram/min), when both drugs were infused simultaneously. Infusion of SSP (0.1, 0.3, and 1 micrograms/min) caused a dose-dependent inhibition of the SNS-induced increases in EPI and NE output. SNS-induced increases in catecholamine output were also inhibited by another PKC inhibitor polymyxin B (PMB 0.1, 0.3, and 1 micrograms/min) and by the phospholipase C (PLC) inhibitor neomycin (NM 0.3, 1, and 3 mg/min). SSP, PMB, and NM did not affect basal output of EPI and NE. These results suggest that activation of PKC promotes release of adrenal catecholamines and provide indirect evidence that activation of PKC and PLC may be involved in SNS-induced release of catecholamines from dog adrenal gland.

Adrenal Glands↗

Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes.

A circulating form of the membrane-bound ICAM-1 (CD54), a ligand for lymphocyte function-associated antigen-1 (LFA-1), has recently been identified in normal human serum. In this study, serum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis and chronic active hepatitis (autoimmune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC, sICAM-1 levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controls. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-1, investigation of ICAM-1 gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-1 mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may be an important source of sICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.

Adolescent↗

Cultural anthropology approach to psychopathology of Muslim murderer.

We report a case involving a 31-year-old Islamic male who murdered his associate under particular circumstances. We took the opportunity to test psychiatrically this man who has been diagnosed in his mother country as a schizophrenic. He came to Japan and was working as a laborer. He is an earnest practicing Muslim. We took an interest in this case because of his bizarre behavior previous to the actual crime. We are interested in the actual method of the murder in relation to Mr. A's cultural and religious background. We demonstrated the significance of the religious cultural knowledge relative to the indigenous ritual for expelling satan and the Islamic pilgrimage to Mekka (Hajj). We conclude that a cultural anthropological and religious viewpoint is necessary in objectively understanding the sources of suffering in patients with mental illness who are from foreign countries.

Adult↗

Identification and characterization of genes encoding polycyclic aromatic hydrocarbon dioxygenase and polycyclic aromatic hydrocarbon dihydrodiol dehydrogenase in Pseudomonas putida OUS82.

Naphthalene and phenanthrene are transformed by enzymes encoded by the pah gene cluster of Pseudomonas putida OUS82. The pahA and pahB genes, which encode the first and second enzymes, dioxygenase and cis-dihydrodiol dehydrogenase, respectively, were identified and sequenced. The DNA sequences showed that pahA and pahB were clustered and that pahA consisted of four cistrons, pahAa, pahAb, pahAc, and pahAd, which encode ferredoxin reductase, ferredoxin, and two subunits of the iron-sulfur protein, respectively.

Amino Acid Sequence↗

Bronchioloalveolar adenoma of the lung: CT-pathologic correlation.

PURPOSE: To correlate the appearance of bronchioloalveolar adenoma (BAA) of the lung at computed tomography (CT) with its pathologic features. MATERIALS AND METHODS: Nine small pulmonary nodules with ground-glass attenuation were found at CT in 668 patients with lung carcinoma. Seven of these nine lesions were histopathologically diagnosed as BAA in four patients (three men and one woman, aged 66-77 years) (three lesions in one man, two lesions in the woman, and one lesion each in the remaining two men) and are the subject of this study. RESULTS: BAA of the lung appeared at CT as a small pulmonary nodule with ground-glass attenuation; microscopic examination revealed hyperplasia of the alveolar cuboidal cells on hyperplastic alveolar septa. The CT findings depicted partial reduction of the alveolar air spaces owing to an increase in cellular components within the lesion. Adenocarcinoma cells were also seen within the BAA lesion in one patient. CONCLUSION: In a patient with known lung carcinoma, a small nodule with ground-glass attenuation simulating a focal lesion of pulmonary interstitial disease must be investigated to rule out BAA or multicentric adenocarcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗

Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.

The Ca2+ responsiveness of vascular smooth muscle myofilaments is not unique: it is increased during neuro-humoral activation and decreased during beta-adrenergic stimulation. In this study we tested whether an augmented Ca2+ responsiveness of smooth muscle myofilaments may contribute to the increased coronary tone observed in hypertension using beta-escin-permeabilized coronary arteries from 3-mo-old stroke-prone spontaneously hypertensive rats (SHRSP) and their age matched normotensive reference strain (WKY rats). In intact coronary arteries, the response to 5-hydroxytryptamine (5-HT) but not to KCl was larger in SHRSP than in WKY rats. In beta-escin permeabilized coronary arteries in which the receptor effector coupling is still intact, 5-HT enhanced force at constant submaximal (Ca2+) (pCa 6.38) to a greater extent in SHRSP. The Ca2+ sensitizing effect of 5-HT was mimicked by GTP gamma S (0.01-10 microM); again this effect was larger in SHRSP. In the absence of 5-HT or GTP gamma S the Ca2+ force relation was similar in both groups. Forskolin induced relaxation at constant submaximal (Ca2+). This desensitizing effect was smaller in SHRSP than in WKY rats. In conclusion, this study shows that intracellular signalling pathways involved in modulating the Ca2+ responsiveness of coronary smooth muscle myofilaments are altered in the genetically hypertensive animals favoring a hypercontractile state in the coronary circulation.

Actin Cytoskeleton↗

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗

The induction of interleukin-6 (IL-6) and colony-stimulating factors (CSFs) by FK565 and its thrombopoietic activity following in vivo administration.

The induction of macrophage colony-stimulating factor (M-CSF) in monkey plasma following administration of FK565 was observed within 2 h of injection peaked at 4 h, and remained high after 24 h. Interleukin-6 (IL-6) and M-CSF levels increased in monkeys treated with FK565, even at doses as low as 0.01 mg/kg. Granulocyte CSF (G-CSF) levels increased slightly following a dose of 1 mg/kg, but granulocyte macrophage CSF (GM-CSF) was not detected at any doses of FK565 studied. To examine the thrombopoietic activity of FK565 in vivo, single doses of drug (0.01, 0.1 or 1.0 mg/kg) were administered i.v. to cynomolgus monkeys or normal mice on day 0. The promotes platelet (PLT) count after FK565 injection decreased transiently on days 1 and 2, and then increased in a dose-dependent manner on day 5 and was still high on day 14. The experiment using anti-PLT antibody showed that the increased PLT count was not simply due to a rebound phenomenon after the transient decrease in PLT. The effect of i.v. FK565 was studied in mice myelosuppressed with a single dose of mitomycin C (MMC) (5.6 mg/kg). The fall in PLT count was suppressed on day 7 by 0.1 and 1.0 mg/kg FK565. Although intact cells or tissues are necessary for an increase in PLT following FK565 treatment, FK565 suppressed the impaired hematopoietic function seen after chemotherapy. FK565 is proposed as a drug to restore reduced neutrophil and platelet counts found in AIDS or cancer therapy.

Animals↗

Purification and characterization of a membrane-bound ATPase from Acetabularia cliftonii that corresponds to a Cl(-)-translocating ATPase in Acetabularia acetabulum.

A Mg(2+)-ATPase was solubilized from membranes of Acetabularia cliftonii using nonanoyl-N-methylgluconamide and purified by ion-exchange and gel permeation chromatography. One active ATPase fraction after Mono Q chromatography had a specific activity of 10 units/mg of protein. Judged from subunit composition [54 (a), 50 (b) with a fainter band around 40 kDa], catalytic properties, and N-terminal amino acid sequence of the b subunit, the isolated enzyme was comparable to the Cl(-)-ATPase of Acetabularia acetabulum. Immunological characterization of both subunits showed significant similarity to the F type of ATPase. Cl(-)-transport activity was observed by reconstitution studies into liposomes.

Acetabularia↗

Chloroplast ATPase in Acetabularia acetabulum: purification and characterization of chloroplast F1-ATPase.

ATPases were isolated from chloroplasts of the unicellular marine alga Acetabularia acetabulum. Two preparations of ATPase, a chloroplast-enriched fraction and an alpha beta gamma-complex were compared. The alpha beta gamma-complex was released into an EDTA solution and purified by anion-exchange chromatography, hydrophobic chromatography, and gel permeation chromatography. The subunit composition of this enzyme appeared to be 52-53 (alpha), 51 (beta), and 40 (gamma) kDa from SDS-PAGE. ATPase activity was enriched about 260-fold to a specific activity of approximate 4.1 U.mg protein-1. The catalytic properties of the alpha beta gamma-complex were as follows: pH optimum at 7.5; substrate specificity, ATP > ITP, GTP > UTP = CTP (Km for ATP 0.2 mM); divalent cation requirement, Mg2+ = Mn2+ = Co2+ > Zn2+ > Ni2+ > Ca2+; ATPase activity was inhibited by monovalent anions (NO3-, SCN-), while monovalent cations had neither inhibitory nor stimulatory effect. Orthovanadate had no inhibitory effect on the enzyme activity of alpha beta gamma-complex. Azide was the most effective inhibitor of the alpha beta gamma-complex. N-Terminal amino acid sequences of the alpha and beta subunits were not obtained and appeared to be blocked. The gamma subunit gave a sequence of AGLKEMKD-XIGSVXNTKKI, which showed 60% similarity to the gamma subunits of spinach and Chlamydomonas reinhardtii CF1-ATPase and EF1-ATPase.

Acetabularia↗

Flow cytometric analysis of the cell cycle of the leukemic cell lines treated with etoposide and cytosine arabinoside.

Effects of etoposide (VP-16) and cytosine arabinoside (Ara-C) on the cell cycle of HL-60 and THP-1 cells were studied by flow cytometry using the bromodeoxyuridine (BrdU)/DNA assay technique to investigate the efficacy of VP-16 for monocytic leukemia cells. VP-16 inhibited the proliferation of THP-1 cells more strongly than that of HL-60 cells at any concentrations used at 24 and 48 hr. VP-16 arrested HL-60 and THP-1 cells in the G2/M phase and reduced them in the G0/G1 and early S phase at higher concentrations. There was no significant difference in the percentage of G2/M phase cells at the same concentration between both cells. However, reduction in the G0/G1 and early S phase cells was more marked in THP-1 than HL-60 cells significantly. On the other hand, Ara-C perturbed the cell cycle of HL-60 cells more than that of THP-1 cells at 24 and 48 hr. These results suggest that the effects of VP-16 on the cell cycle may be more intense in THP-1 than HL-60 cells, and support the efficacy of VP-16 for treating monocytic leukemia in vivo.

Bromodeoxyuridine↗

[A study of relationships among solvent inhalation, personality and expectancy; especially on affinity to hallucination, sensation seeking and neurotic tendency].

94 delinquents in two homes for resocialization were surveyed to elucidate the relationship among the status of volatile solvent inhalation, expectancy and personality. The subjects were classified into solvent-inhalation group and non-solvent-inhalation group, and the former was divided into solvent dependence group and abuse group according to DSM-III-R. Each group was given personality tests; general health questionnaire (GHQ), sensation seeking scale (SSS), the vividness of visual imagery (VVIQ), test of visual imagery control (TVIC) and Yatabe-Guilford test (YG). In addition we investigated expectancy and mental symptoms caused by inhalation in it. The results are summarized as follows; 1. Inhalation group scored higher on SSS than non-inhalation group. 2. Compared with abuse group, dependence group presented with 1) higher GHQ score meaning neurotic tendency; 2) higher TVIC score meaning imagery-control-ability; 3) a higher incidence of day-dream and hallucination, especially egosyntonic type; 4) higher expectancy of "enhancement of positive affection", "reduction of negative affection" and "hallucination seeking"; 5) lower expectancy of "association with friends". 3. Higher scored inhalers on TVIC showed visual hallucinations, especially egosyntonic type more frequently than lower ones. 4. Significant correlations were recognized between GHQ score and expectancy of "reduction of negative affection", and between lack of objectiveness score of YG subscale and "hallucination seeking" expectancy. These results suggested that 1) beginning of inhalation is associated with sensation seeking trait, 2) progression to solvent dependence is correlated with three expectancies, i.e., seeking egosyntonic hallucinations paralleling high imagery-control-ability and subjectivity, reducing negative affection paralleling neurotic tendency, and enhancing positive affection. According to the findings, indulgence to drug induced positive imagery led delinquents into splitting of personality. In their treatment we need to help them to integrate high imagery ability and sensation seeking for recovery.

Adolescent↗

Proinflammatory cytokines and endotoxin stimulate ICAM-1 gene expression and secretion by normal human hepatocytes.

Hepatocytes in normal tissues express low or undetectable levels of intercellular adhesion molecule-1 (ICAM-1), as detected by immunohistochemistry. Up-regulation of ICAM-1 expression on these cells has been reported in inflammatory liver disease (hepatitis B virus infection, autoimmune liver disorders and liver allograft rejection), and the molecule has been implicated in the recruitment, retention and activation of inflammatory cells. There is, however, little information concerning the regulation of hepatocyte expression of ICAM-1. We show here, for the first time, the induction (within 30 min) of ICAM-1 gene expression in cultured normal human hepatocytes stimulated with interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) or endotoxin. IFN-gamma was the most potent single inducer (up to fourfold at 6 hr), while further induction of ICAM-1 mRNA was achieved with cytokine combinations. Maximal mRNA expression was achieved within 10 hr. ICAM-1 could be detected readily by immunocytochemical staining on the hepatocyte surface by 12 hr, and by enzyme immunoassay in the culture medium by 24 hr. The data present clear evidence that cytokines, which have been implicated previously in inflammatory liver diseases, can up-regulate directly both ICAM-1 gene expression and protein secretion/shedding by human hepatocytes.

Base Sequence↗